SINGLE-DOSE PHARMACOKINETICS OF PARACETAMOL AND ITS CONJUGATES IN CHINESE NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH RENAL IMPAIRMENT

Objective: A single oral dose of paracetamol (20 mg . kg(-1)) was give n to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of ren al impairment, with creatinine clearances ranging from 4 to 123 ml . m in(-1) 1.73 m(-2). The plasma and urinary concentrations of paracetamo l and its major metabolites were measured by high-performance liquid c hromatography (HPLC). Results: The absorption and elimination of parac etamol were unaffected by renal impairment. However, the area under th e plasma concentration time curve and the elimination half-life of par acetamol metabolites increased significantly with worsening renal insu fficiency. Mean renal clearances of paracetamol and its conjugates wer e significantly reduced in these subjects. There was no evidence of al tered metabolic activation with renal impairment. Conclusion: The resu lts demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates ma y occur.